The myocardial cell and its microvascular bed will be explored in order to 1) define the effects and interactions of aging and hypertension, and 2) establish the long-term effects of antihypertensive drug therapy and the regression of cardiac hypertrophy. Comparisons between the Wistar-derived Okamoto-Aoki strain of spontaneously hypertensive rats (SHR) and their normotensive Firth-Wistar controls will be made at various ages during their life-span. The experiments, by incorporating various morphological and physiological approaches, are designed to correlate structural and functional parameters. Our previous work provides evidence that long-term hypertension and hypertrophy accelerate and magnify aging of the myocardium. Three major avenues of research are currently being pursued: 1) the determination of regional myocardial blood flow, vasodilatory reserve, and reactive hyperemia, in unanesthetized rats; 2) studies on the mechanism of cardiac hypertrophy in SHR; and 3) studies on the regulation of specific cellular organelles during hypertrophy and aging. We will utilize various surgical and drug interventions and study the myocardium with electron microscopy in conjunction with morphometry, cytochemistry, and radio active microspheres. These approaches are consistent with our goal to define the response of the myocardial cell and its microvascular bed to systemic hypertension.